2-furaldehyde

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline animal experimental study, published in peer reviewed literature, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The toxicokinetics of furfuryl alcohol and furfural were determined in rats following oral administration.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

furfural

IUPAC Name:

furfural

Constituent 2

Reference substance name:

Furfuryl alcohol

EC Number:

202-626-1

EC Name:

Furfuryl alcohol

Cas Number:

98-00-0

Molecular formula:

C5H6O2

IUPAC Name:

2-furylmethanol

Details on test material:

[Methylene-14C]-furfuryl alcohol and [carbonyl-14C]-furfural, 4.1mCi/mmol, 97% & 95% radiochemically pure was purchased from Mew England Nuclear, Boston, MA.
Furfuryl alcohol, 99% pure and furfural, 99% pure were purchased from Aldrich Chemical Co., Milwaukee, WI.

Radiolabelling:

yes

Remarks:

[carbonyl-14C]-furfural & methylene-14C-furfuryl alcohol

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

- Source: Charles River Breeding Laboratories, Kingston, NY.
- Age at study initiation: 11 weeks
- Weight at study initiation: 198-248g
- Housing: Collection of excreta/tissues - Nalgene metabolism cages (Nalge Co., Rochester, NY). Collection of expired air - Roth glass metabolism cages (Crown Scientific Glass Co., Orland Park, IL).
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Purina Rodent Chow #5002 (Raltech Scientific Services, St. Louis, MO) ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1
- Humidity (%): 37-66
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

(dosing volume 5 ml/kg)

Duration and frequency of treatment / exposure:

Single oral dose

Doses / concentrations

Remarks:

Doses / Concentrations:
Furfuryl alcohol: 0.275, 2.75, 27.5 mg/kg
Furfural: 0.127, 1.15, and 12.5 mg/kg

No. of animals per sex per dose / concentration:

4

Control animals:

no

Positive control reference chemical:

no

Details on dosing and sampling:

The expired air was passed through charcoal traps followed by potassium hydroxide traps and collected at 0-4, 4-8, 8-18, 18-25 and 25-42 hr. Urine and feces were collected at 0-4, 4-8, 8-24, 24-48 and 48-72 hr following administration. Urine and feces were kept frozen during collection. A thorough cage wash with water was performed at the time of sacrifice. Rats were anesthesized with sodium pentobarbital (~70-80 mg/kg ip) at 72 hr and blood (~5 ml) was recovered by cariac puncture and transformed to heparinized Vacutainer tubes (Becton Dickinson & Co, Rutherford, NJ). Plasma and blood cells were obtained by centrifugation and kept on ice prior to freezing at -20C. Tissues were removed, weighed, and immediately frozen on ice and stored at -20C until analysis. Tissues, feces, charcoal and urine samples were analysed for total radioactivity.

Statistics:

no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

At least 86-89% was absorbed at all doses studied.

Details on distribution in tissues:

Both furfuryl alcohol and furfural showed similar patterns of distribution. Liver and kidney contained the highest concentration of radioactivity and brain the lowest. Concentrations were proportional to the dose.

Details on excretion:

86-89% of the dose was excreted in urine, the majority within 24 hr. The percentage of dose excreted in the urine was unaffected by dose over the range studied. 2-4% was excreted in the faeces. Approx. 94-96% of the doses were recovered at all doses investigated.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

No unchanged furfuryl alcohol or furfural was detected in urine. The major urinary metabolites were furoylglycine (73-80%), furoic acid (1-6%) and furanacrylic acid (3-8%). The extent and rate of excretion of the metabolites were independent of dose.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: bioaccumulation potential cannot be judged based on study results

Executive summary:

Approximately 88% of an oral dose of either furfuryl alcohol or furfural were absorbed. The major route of excretion was in urine. No unchanged furfuryl alcohol or furfural were detected; the major urinary metabolite was furoylglycine with lesser amounts of furanacrylic acid and furoic acid. The highest tissue concentrations were in liver and kidney. Absorption, extent and route of metabolism and excretion rates were all independant of dose over the range studied.